Studying male MZ and DZ like-sex twin pairs prospectively permits powerful tests of hypotheses about individual characteristics that are mediators of genetic and environmental influences on adolescent drinking problems and alcoholism risk, as well as of hypotheses about risk- modifiers. Cohorts of male like-sex pairs aged 15, 15, 17, 19 and 21 (n=1853 families over 5 years) will be ascertained from Missouri state birth records and traced, using a cohort-sequential sampling design. A high-risk sample, identified by maternal telephone interview as having a biologic parent with a history of alcohol dependence, and a control sample, will be assessed by telephone interview and self-report questionnaire and followed prospectively with annual assessments (392 MZ, 322 DZ pairs). Analyzed in conjunction with data on cohorts of female-like sex adolescent pairs. These data will permit tests of key hypotheses about mediators of alcoholism risk and their consistency across gender, including (i) the interrelationship between different measures of behavior under-control (childhood inattention and hyperactivity, oppositional and conduct problems, school failure) and risk of alcohol problems; (ii) the role of nicotine dependence as a 'gateway' addiction and mediatory of the association between depression and alcoholism risk; (iii) the importance of alcohol-specific genetic effects, including genetically determined differences in self-report initial tolerance to alcohol; (iv) the role of perceived peer behaviors as mediators as mediators of genetic influences associated with behavioral under-control (genotype-environment correlation); (v) the interaction of genetic differences with environmental protective factors (family religious involvement, positive parenting: genotype environment interaction). In conjunction with other projects (family study offspring of alcoholism-discordant twin pairs), these data will offer a unique opportunity to study environmental and genetic mediators of alcoholism risk as a function of gender and ethnicity, and the interaction with protective factors.